"There is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant." Alexander Fleming said this during his Nobel prize acceptance speech in 1945, almost two decades after discovering penicillin and heralding in the antibiotic era, changing the course of modern medicine. 70 years later, Fleming is sadly right. Through underdosing, overusing, counterfeiting and generally misusing antibiotics, the ignorant man is indeed now faced with rampant worldwide antibiotic resistance.
In a Nesta survey, antibiotic resistance was considered by the public as the UK's biggest health threat. Such resistance occurs when bacteria that cause infection survive exposure to a medicine that would normally kill them or stop their growth. It means the drugs don't work. Although this would naturally happen due to biological evolution of the bacteria, it is exacerbated by factors like misuse of medicines, poor infection control and travel. It is a global problem, but its causes, consequences and management vary widely across different parts of the world.
"The healthcare systems we see in Europe are very different from the healthcare systems we see in developing countries, and it's not just the infrastructure but also access to those systems," says Dr Manica Balasegaram, Executive Director of the Access Campaign at Médecins Sans Frontières (MSF). "Ways in which you control antibiotics in Europe are not always relevant to places where healthcare systems are poor."
Those systems are very different, and in many cases, very broken. A New York Times reporter visited neonatal intensive care units in five states in India last year and found doctors overwhelmed by the number of babies suffering from multi-drug-resistant infections. In one hospital in New Delhi, this was the case for "close to 100 per cent of referrals". The consequences are devastating, with 58,000 babies dying in India of resistant infections in 2013: more than 150 every day. By comparison, an estimated 25,000 people die every year in Europe from antibiotic-resistant bacteria, according to a report in the Lancet. It's still a high figure, but it highlights the heavier magnitude of the problem that antibiotic resistance poses to weakened healthcare systems.
In developing countries, the main drivers of resistance are high burdens of infectious diseases resulting from improper prevention, availability of substandard drugs, insufficient or poorly trained health personnel, and little access to diagnostics to test infections. In these settings, inappropriate use of antibiotics is also defined by access to them. In some parts of the world, including sub-Saharan Africa, access to antibiotics is simply limited due to drugs not reaching the marketplace at all, or being unaffordable for most. In some Asian countries, however, people who do purchase antibiotics might be unknowingly consuming substandard, falsified or counterfeit drugs, which might just contain enough antibiotic to teach the bacteria how to resist it.
But if resistance arises from overusing antibiotics, how does lack of access to them contribute to resistance? The answer lies in quality and regulation. According to the Lancet, increasing access without implementing other measures is not desirable in parts of Asia, for example, where most antimicrobial drugs are produced and where overuse is common. In low and middle-income countries, however, where people have little access to drugs or aren't able to afford a full course of treatment, and can only obtain substandard drugs to which bacteria are already resistant, increasing access to quality drugs can reduce selection pressure to develop resistance.
Increasing access to quality antibiotics, however, is only one part of the solution. In fact, the BRICS countries had the greatest increases in antibiotic use between 2000 and 2010: 68 per cent in Brazil, 19 per cent in Russia, 66 per cent in India, 37 per cent in China and a staggering 219 per cent in South Africa. This points to drugs not only being accessible, but also being needed, or at least perceived as needed. That underlines two crucial strategies that developing countries must still implement if they wish to be antibiotic stewards: health promotion and disease prevention. And below these is the holy trinity of global health: water, hygiene and sanitation.
As many as 2.3 billion people don't have access to a safe and private toilet, according to charity WaterAid. In South Sudan, this is the case for 91 per cent of the population. 650 million people worldwide don't have access to safe drinking water. These conditions make it far too easy for disease to spread, increasing the need for drugs. Indeed, according to a report by the Center for Disease Dynamics, Economics and Policy, a key national policy to change antibiotic use is to improve access to clean water and sewerage systems.
Access to clean water and sanitation is also one of the Sustainable Development Goals adopted this year. Although antibiotic resistance isn't addressed directly in those goals, this year's World Health Assembly endorsed a global antibiotic resistance action plan, with World Health Organisation member states expected to have plans in place by 2017. At the country level, the Chennai Declaration offers a roadmap to tackle the problem in India. Lead author Dr Abdul Ghafur warns, however: "unrealistic recommendations will lead to complete failure of policy."
Cultural context is key to any health intervention. Dr Balasegaram recalled an MSF survey in Afghanistan that indicated people saw antibiotics as an integral part of their healthcare system, which is "very weak and in parts non-existent. So you cannot come there and say we want to take away antibiotics, because in a way you're effectively saying you're taking a crucial element of their healthcare system."
This is where health education comes in. Global Antibiotic Resistance Partnership (GARP) working groups in India and Kenya, for example, run activities like antibiotic stewardship workshops, policy forums, and open online courses to educate healthcare workers and policy makers.
Diagnostic tools are another important piece of the resistance puzzle, and innovative thinking is needed around access in different healthcare settings. There is hope to be had by looking at Rapid Diagnostic Tests (RDT) for malaria and GenExpert for tuberculosis. In Zambia, access to point-of-care RDTs led to a fourfold reduction in inappropriate antimalarial prescribing for children and a fivefold increase in appropriate use of antibiotics for pneumonia. Initiatives like the Longitude Prize are hoping to provides incentives for creative minds worldwide to come up with a diagnostic tool that is affordable and can be used in resource-poor settings. The five-year competition runs until 2019.
In the meantime, small things in our daily lives could help prevent the spread of resistant germs. The US Centres for Disease Control and Prevention recommend washing our hands for as long as it takes to sing the Happy Birthday song twice. With the future of modern medicine at stake, it's time well spent.